Loffet Elise A, Durel John F, Kam Richard, Lim Hyunjee, Nerurkar Nandan L
Department of Biomedical Engineering, Columbia University, New York NY 10027.
bioRxiv. 2023 Jul 19:2023.07.18.549562. doi: 10.1101/2023.07.18.549562.
During embryonic development, tissues must possess precise material properties to ensure that cell-generated forces give rise to the stereotyped morphologies of developing organs. However, the question of how material properties are established and regulated during development remains understudied. Here, we aim to address these broader questions through the study of intestinal looping, a process by which the initially straight intestinal tube buckles into loops, permitting ordered packing within the body cavity. Looping results from elongation of the tube against the constraint of an attached tissue, the dorsal mesentery, which is elastically stretched by the elongating tube to nearly triple its length. This elastic energy storage allows the mesentery to provide stable compressive forces that ultimately buckle the tube into loops. Beginning with a transcriptomic analysis of the mesentery, we identified widespread upregulation of extracellular matrix related genes during looping, including genes related to elastic fiber deposition. Combining molecular and mechanical analyses, we conclude that elastin confers tensile stiffness to the mesentery, enabling its mechanical role in organizing the developing small intestine. These results shed light on the role of elastin as a driver of morphogenesis that extends beyond its more established role in resisting cyclic deformation in adult tissues.
在胚胎发育过程中，组织必须具备精确的物质特性，以确保细胞产生的力能形成发育中器官的定型形态。然而，发育过程中物质特性是如何建立和调控的问题仍未得到充分研究。在这里，我们旨在通过研究肠道成环来解决这些更广泛的问题，肠道成环是指最初笔直的肠管弯曲成环的过程，从而使肠管能够在体腔内有序排列。成环是由于肠管在附着组织——背系膜的约束下伸长所致，背系膜被伸长的肠管弹性拉伸至其长度的近三倍。这种弹性能量储存使系膜能够提供稳定的压缩力，最终使肠管弯曲成环。从对系膜的转录组分析开始，我们发现在成环过程中细胞外基质相关基因广泛上调，包括与弹性纤维沉积相关的基因。结合分子和力学分析，我们得出结论，弹性蛋白赋予系膜拉伸刚度，使其在组织发育中的小肠过程中发挥机械作用。这些结果揭示了弹性蛋白作为形态发生驱动因素的作用，这一作用超出了其在成年组织中抵抗循环变形的既定作用。
